Imaging vascular calcifications in the brain, a collaboration spanning continents and millennia

What could be more fascinating than to explore the prevalence of cardiovascular disease in populations as diverse as ancient mummies, modern Americans, and people living a subsistence lifestyle in Bolivia? That’s been the work of Dr. M Linda Sutherland over the past 19 years, as part of a multidisciplinary and multinational team of specialists, the Horus Team. The newest chapter of this work involves looking closer at the brain health of native populations in Bolivia. For this, Dr. M Linda Sutherland is supported by Dr. Giuseppe Barisano. Their work focuses on interpreting brain scans from 1,000 people from the Tsimane and Moseten populations, in order to analyse calcification of the intracranial internal carotid artery, which can be related to dementia. Analysing this massive dataset could have represented several years of work for a specialised neuroscientist like Dr.  Barisano. But Giuseppe and his team benefited from the expertise of Euro-BioImaging’s Population Imaging Node in Rotterdam to find tools and approaches to make this task easier. Thanks to their collaboration, the data were analysed in less than a year. We spoke to M Linda and Giuseppe to learn more. 

M Linda Sutherland is a medical physician with a background in diagnostic radiology, trained at the University of California, Los Angeles, and was in private practice in Southern California when she became a member of the Horus Team studying cardiovascular disease in mummies in 2005. She has been involved in a number of fascinating projects to better understand cardiovascular disease, and now brain health, across continents and millennia. One of her earlier studies involved scanning the hearts of ancient mummies to identify Atherosclerosis and comparing the findings to Atherosclerosis in modern populations.

From mummies to indigenous populations

She was also part of the scientific team investigating coronary atherosclerosis in indigenous South American Tsimane  and Moseten populations, whose active lifestyle and healthy diet seems to keep them from developing heart disease. Impressed by these findings, her work shifted to studying brain health in the Tsimane and Moseten populations, trying to understand whether these indigenous people would be less subject to dementia than Western populations. She met Giuseppe Barisano, a medical doctor trained in Italy and now a post-doctoral researcher at Stanford University, in Los Angeles in 2017, when he was doing his PhD at the University of Southern California.  He was very interested in her project and a collaboration was established.

“The brain is my area of expertise,” explains Giuseppe. “Linda’s project brings together both of my specialities - as a physician, and as an imaging scientist – in a large population study.” 

One challenge to the next

But this is not just a population study. What gives this study a unique twist is that the study group is composed of individuals living a subsistence lifestyle with no electricity or running water. They live in a remote location, quite far from the nearest hospital. “Our study involves a lot of logistics,” explains M Linda. “The CT scanner is in Trinidad, Bolivia, and it can take several days for some of the participants to get there from their remote villages.   We started the scanning in 2014 with teams from the United States, but this was very time consuming. In the spring of 2024, we set up a protocol with local staff in Bolivia who do the data collection/scanning. The team is able to scan six patients a day, resulting in approximately 1,000 patients a year.”

The CT scanning is  done without contrast, and acquired using the same standard protocol.  A sophisticated wifi system makes it possible to transfer data from the hospital in Trinidad, Bolivia, to M Linda and Giuseppe in California, via a server in Chile. 

The blood vessel Giuseppe needed to identify and study goes through a bone. And to make things worse, the density of calcification is similar to bone. The difficulty of this task was very challenging.”

• Dr. M Linda Sutherland

The data collection is complex, but the data analysis is even more difficult. That’s where Giuseppe comes in. The intracranial internal carotid artery is the most important artery carrying blood to the brain. To measure the vascular calcification in the intracranial carotid artery, Giuseppe needed to find a tool that would allow him to identify the regions of the blood vessels they are interested in, measure the density and volume of the calcifications, and analyse the resulting data. No such tool is available in the standard radiologist toolkit. 

This project has been a really good experience for me. I am happy to expand my technical capacities in terms of neuroimaging and data analysis and the experience of leading a small team was also great.”

• Dr. Giuseppe Barisano

Support from Euro-BioImaging’s Population Imaging Node

In the literature, M Linda and Giuseppe found a study that was similar to theirs, led by Dr. Bos of ERASMUS MC in the Netherlands. He used a custom-made plugin for ImageJ, an open source tool that is commonly used by biologists, in order to analyse intracranial arteriosclerosis in a large population study of 2,339 individuals. They contacted Dr. Bos in order to learn more about the ImageJ tool, and he told him about the Population Imaging Flagship Node - Rotterdam, part of Euro-BioImaging. Through Euro-BioImaging, the custom ImageJ plugin was provided and Giuseppe was trained on how to use it  to study the intracranial internal carotid artery. Giuseppe was able to master the tool quite quickly. “Having a background in neuroimaging helped. Overall, the custom ImageJ tool was really easy to learn how to use - even virtually,” claims Giuseppe. 

The next challenge was to perform the task. “The blood vessel Giuseppe needed to identify and study goes through a bone. And to make things worse, the density of calcification is similar to bone,” explains M Linda. “The difficulty of this task was very challenging.”

“There are two challenges with this task,” explains Giuseppe. “One is related to neuroanatomy knowledge and the other is the sheer volume of images to analyse.”

Analysing the scans

Giuseppe recruited a team of 3 graduate students to help him perform the task and trained them in ImageJ. Together they worked for one year to analyse the scans, and another to prepare the final analysis and manuscript, which was submitted in 2024.

“This project has been a really good experience for me,” says Giuseppe. “I am happy to expand my technical capacities in terms of neuroimaging and data analysis and the experience of leading a small team was also great.”

In parallel,  Giuseppe and his team are now training an AI algorithm, which will simplify the calcification assessment in the future, using the background data they acquired. 

“I am very interested in the AI aspects and training of the model,” says Giuseppe. “Not only could it be very helpful in developing future applications in the clinical world, but also opens a career perspective for me.”

Towards artificial intelligence tools

This study has potential to be a game changer – both for Giuseppe’s career but also for the field of neuroimaging.  The fruits of this work – employing some of society’s most modern technologies and tools - may help to reveal some lessons from the past - in terms of the link between diet, lifestyle and heart health, brain health, and longevity.